NM_001195605.2:c.878C>G

Variant names:

• chr19-55614496-C-G
• rs1188216751
• NM_001195605.2:c.878C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195605.2(ZNF865):​c.878C>G​(p.Pro293Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P293L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF865 NM_001195605.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.497
• Publications: 0 publications found

Genes affected

ZNF865 (HGNC:38705): (zinc finger protein 865) Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12838465).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195605.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF865	NM_001195605.2	MANE Select	c.878C>G	p.Pro293Arg	missense	Exon 2 of 2	NP_001182534.1	P0CJ78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF865	ENST00000568956.2	TSL:2 MANE Select	c.878C>G	p.Pro293Arg	missense	Exon 2 of 2	ENSP00000457715.1	P0CJ78
	ZNF865	ENST00000870148.1		c.878C>G	p.Pro293Arg	missense	Exon 3 of 3	ENSP00000540207.1
	ZNF865	ENST00000870149.1		c.878C>G	p.Pro293Arg	missense	Exon 2 of 2	ENSP00000540208.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	7.3
DANN	Benign	0.25
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.36	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.13	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.50
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.39	N
Sift	Benign	0.49	T
Sift4G	Uncertain	0.0030	D
Vest4		0.15
MVP		0.35
GERP RS		0.12
Varity_R		0.029
gMVP		0.18
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1188216751; hg19: chr19-56125862;